Telomerization terminator

Greider, C. W., and Blackburn, E. H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405 13. 

Telomerase (also AKA telomere terminal transferase) extends the 3 ends of a chromosome by adding numerous repeats of a six base pair sequence until the 3 end of the lagging strand is long enough to be primed and extended by DNA polymerase (Fig 11.26). 

The problem of telomere shortening is solved by an enzyme that adds telomeric sequences to the ends of each chromosome. The enzyme is a protein and RNA complex called telomere terminal transferase, or telomerase. Because the sequence of the telomerase-associated RNA, as we will see, serves as the template for addition of deoxyribonucleotides to the ends of telomeres, the source of the enzyme and not the source of the telomeric DNA primer determines the sequence added. This was proved by transforming Tetrahy mena with a mutated form of the gene encoding the... 

Two distinct but related strategies that rely on templates to control the number of monomers incorporated into an oligomeric product can be envisioned. One of these approaches, shown in Scheme 8-2, relies on templated radical macrocyclization reactions to control telomer size [14, 15]. This strategy requires attachment of all of the monomer units to the template backbone and uses macrocyclization, which faces competition from intermolecular chain transfer, to control the telomer length. The chain transfer agent T-I (i.e., telomerization terminator) is not attached to the template. 

G. B. Morin, The human telomere terminal transferase enzyme is a ribonu-cleoprotein that synthesizes TTAGGG repeats, CeU, 59, 521, 1989. 

Telomere Terminal region of a linear chromosome, containing partial single-stranded DNA and repeat sequences of short oligonucleotides. Its loss could cause chromosome fusion and rearrangement. 

Butadiene telomerization using nitroethane as a trapping reagent is applied to the total synthesis of the natural product, recifeiolide, where the secondary nitro group is converted into the ketogroup by the Nef reaction, and the terminal double bond is converted into the iodide via hydro alumination (Scheme 5.6).71... 

Hydrogenation of the lateral chain of telomerized polysaccharides (starch, inulin) has been carried out using homogeneous RhCl(TPPTS)3 complex (0.8%) at40°C under 30 atm. H2 in H20/EtOH (5/1) mixture. Both terminal and substimted double bonds were successively hydrogenated [59]. 

The termination of replication on linear eukaryotic chromosomes involves the synthesis of special structures called telomeres at the ends of each chromosome, as discussed in the next chapter. 

Although various transition-metal complexes have reportedly been active catalysts for the migration of inner double bonds to terminal ones in functionalized allylic systems (Eq. 3.2) [5], prochiral allylic compounds with a multisubstituted olefin (Rl, R2 H in eq 2) are not always susceptible to catalysis or they show only a low reactivity [Id]. Choosing allylamines 1 and 2 as the substrates for enantioselective isomerization has its merits (1) optically pure citronellal, which is an important starting material for optically active terpenoids such as (-)-menthol, cannot be obtained directly from natural sources [6], and (2) both ( )-allylamine 1 and (Z)-allylamine 2 can be prepared in reasonable yields from myrcene or isoprene, respectively, The ( )-allylamine 1 is obtained from the reaction of myrcene and diethylamine in the presence of lithium diethylamide under Ar in an almost quantitative yield (Eq. 3.3) [7], The (Z)-allylamine 2 can also be prepared with high selectivity (-90%) by Li-catalyzed telomerization of isoprene using diethylamine as a telomer (Eq. 3.4) [8], Thus, natural or petroleum resources can be selected. 

Photolysis of this polymer gives radicals on which side chains can be formed, giving graft polymerization 122, 123, 153). Similarly the polymerization of styrene (152) or vinyl acetate (157) in the presence of bromotrichloromethane gives telomers carrying terminal bromine atoms and trichloromethyl groups. By ultraviolet irradiation (3500 A) in the presence of methyl methacrylate the carbon-bromine links are broken and block copolymers are formed. The telomerization of acrylonitrile and acrylic acid with bromoform is based on the same technique the end groups of both polyacrylonitrile and polyacrylic acid were photolyzed in the presence of acrylamide and afforded polyacrylamide blocks linked to polyacrylonitrile or polyacrylic acid blocks (164, 165). 

In fact, alkylated succinamides were isolated in some cases, though in very poor yields, and result from radical combination, which is a chain termination step. The experimental observations, i.e. the formation of (a) 1 1 adducts, (b) telomeric products, (c) alkylated succinamides, and (d) oxamide (when an olefin is absent), are consistent with a free radical mechanism. The telomeric products obtained support the assumption that we deal here with a chain reaction, because they are characteristic products of this type of reaction. Another proof for the chain reaction mechanism is the fact that when benzophenone is used as a photoinitiator (vide infra), the amount of benzpinacol formed is smaller than the amount of the 1 1 addition product of formamide and olefin (16). Quantum yield determinations will supply extra evidence for the validity of a chain reaction mechanism for this photoaddition reaction. 

As previous reactions have already shown, this reaction seems to be a free radical chain reaction. The experimental evidence so far available for such a mechanism is the following (a) the formation of dehydrodimers in the absence of an olefin (b) the formation of the anti-Mar-kovnikov 1 1 adduct as the major product when a terminal olefin is employed as the addend, and (c) the telomeric products obtained. Thus, reaction sequence can be summarized as follows ... 

The increased reactivity of isocyanates, relative to carbon dioxide, was reflected in the wider range of cycloaddition partners. For example, terminal diynes as well as nontethered alkynes (e.g., 3-hexyne) were also successfully converted to 2-pyridones rather than undergoing rapid telomerization to aromatic by-products. Importantly, the cycloaddition of an asymmetrical... 

Many of the proteins and enzymes involved in initiation at replication origins and DNA chain growth at replication forks have the same biochemical activities as their counterparts in bacteria. However, the situation regarding terminators and terminator proteins is less clear. Whether they exist to delineate to any extent individual replicons or clusters of replicons is not known. In the case of eukaryotic chromosomes, however, there is a special mechanism to replicate their ends which are known as telomeres. 

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